The research presented in this proposal aims to solve one of the major limitations in implant repair of osteochondral defects, namely the control of architecture and morphology of replacement biomaterials. Osteochondral defects have an extremely limited potential for self-repair. Whether the defect is traumatic or degenerative, osteoarthritis frequently results from these defects necessitating surgical repair. Surgical treatment of large osteochondral defects is often accomplished by transferring a non-weight bearing section of bone and cartilage to the defect. This is a costly and invasive procedure without a reliable outcome for patients. An attractive alternative is to replace the defect with a single material that restores lost bone and simultaneously replaces the lost cartilage with material to cushion the compressive, tensile, and shearing forces of joint loading. The innovation in this proposal is novel biofabrication process for creating 3D Nano- cellulose hydroxyapatite biocomposite (Nano-biocomposite) which functions as a load bearing articular cartilage and its underlying bone for repair of large osteochondral defects. Our manufacturing process is capable of producing this unique biomaterial with gradient of properties at large scale, at low cost and with great environmental efficiency. Bacterial cellulose, BC is an emerging nano-biomaterial consisting of cellulose nanofibril networks produced by bacteria Acetobacter xylinum. It is a hydrogel-like biomaterial with unique biocompatibility, mechanical integrity, hydroexpansivity, and stability under a wide range of conditions. The similarity of size of cellulose nanofibrils with collagen makes cellulose an ideal scaffolding material for regenerative medicine. We propose to develop a biofabrication process of gradient 3D Nano- biocomposites for repair of osteochondral defects. We have made innovations with which we can manufacture bacterial cellulose nano-biomaterial with spatially controlled architecture and surface properties. PUBLIC HEALTH RELEVANCE: Reconstruction of orthopedic defects that arise from trauma, disease, age, or congenital defects is a necessary procedure to protect vital organs, restore motor function, and improve patient self-confidence. In the US an estimated 800,000 grafting procedures were performed in 2003 making bone the second most transplanted tissue after blood. Osteochondral defects are among large unmet medical needs. The research presented in this proposal aims to solve one of the major limitations in implant repair of osteochondral defects, namely the control of architecture and morphology of replacement biomaterials.